This study was a randomized double-blinded placebo-control 2-period cross-over clinical drug study to determine the effect of single topical applications of HP-Guar in patients with dry eyes. The effect was measured using the determination of tear evaporative parameters in a laboratory setting where RH could be controlled and varied.
The protocol, consent forms, and data accumulation methods used in these studies were previously approved by the University of Texas Southwestern Medical Center Institutional Review Board. Informed consent was obtained from each patient at screening. HIPAA regulations were followed.
Eligibility requirements for the KCS patients included a prior diagnosis of dry eye with symptoms of foreign body sensation or dryness combined with the findings of interpalpebral fissure conjunctival vital dye staining along with a decreased tear film meniscus on slit-lamp biomicroscopy. Patients were excluded if either eye had clinically evident lid or ocular surface inflammation. None of these patients had active systemic disease or were taking medications that could affect tear production. Subjects were excluded if they were participating in any other investigational therapeutic drug or device trial at the time of enrollment or within the previous 30 days. The enrollees were, however, using a variety of tear replacement topical medications prior to the first studies and in the interval between the studies.
Twelve patients, nine women and three men, were enrolled, ages 51 to 83. They were randomly assigned to either treatment sequence: 1 (Saline then Hp-Guar) or 2 (Hp-Guar and then saline at the second study visit). We evaluated the acute effect of single drop applications of each solution on ocular surface evaporation. There was a 2–14 day interval between 1st and 2nd visits. Evaporative rates were measured at baseline with each test agent, i.e., before the application of any test drop on the eye, and also 30 and 60 minutes after the instillation of one 40μl drop of HP-Guar or saline solution.
Following enrollment and in between the study visits, patients were instructed to continue using their usual dry eye therapy except to stop on the day of the evaluation.
Tear evaporation studies were conducted with an evaporometer (Oxdata, Portland, Oregon) that utilized a pump to direct room air through a drying tube into a form-fitting goggle that created a closed environment and contained a humidity/temperature sensor which has been described in detail elsewhere (10
) Dry air was pumped into the goggle to reduce RH to 15%, at which time the pump was turned off. The RH within the goggle was allowed to rise. The increase in humidity due to evaporation from skin or evaporating tears was measured. Room temperature was maintained in the range of 22–24 °C. The process was carried out first with the eye closed and then with it open; the difference between these two processes determined the ocular surface tear evaporation rate (11
). Using the original formula published by Rolando and Refojo,(12
) we calculated the evaporative rates under two different ranges of increasing RH, 25% to 35% and 35% to 45%. The area of the interpalpebral ocular surface was used to calculate evaporation per unit area; the image of the area was captured with the use of a digital camera, and the area was calculated directly with the aid of computer software (Adobe Photoshop, version 184.108.40.2061; Adobe Systems, San Jose, California), (11
) expressed as μL/cm2
/min. This same sequence of testing was carried out on the day of second testing using a single drop of the opposite test agent.
The data were analyzed in several ways. Within-patient, before and after test agent instillation comparisons in different humidity conditions were conducted using one-sided paired t-tests. Only data from the left eye was used in the calculations. Statistical significance was set to 95% confidence level for all tests. The potential of a therapeutic carry-over effect from the first treatment on the second treatment was evaluated by comparisons between the two different sequence groups using a 2-sided Wilcoxon rank test. Statistical computing was performed using SAS 9.1 (SAS Institute, Cary, NC).